Chen H W, Cavenee W K, Kandutsch A A
J Biol Chem. 1979 Feb 10;254(3):715-20.
Two lines of Chinese hamster lung (Dede) cells which are resistant to the killing effect of 25-hydroxycholesterol, and which grow to confluence in its presence, have been isolated. One of the resistant lines exhibited a high to normal growth rate and normal levels of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (mevalonate:NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34) activity and sterol synthesis in the presence of concentrations of 25-hydroxycholesterol that caused nearly complete suppression of these functions in wild type cells. The other variant line showed partial resistance to the inhibitory effects of the diol upon cell growth, sterol synthesis, and HMG-CoA reductase activity. The resistant phenotypes remained stable when the cells were maintained in the absence of the selecting agent. The Km (HMG-CoA), thermal stability, and susceptibility to inhibition by Mg2+ and ATP of HMG-CoA reductase were unaltered in both of the resistant lines. The two lines selected for growth in the presence of 25-hydroxycholesterol were also resistant to the inhibitory effects of 7-ketocholesterol, 20alpha-hydroxycholesterol, and serum upon HMG-CoA reductase and sterol synthesis, suggesting that suppression of cholesterol synthesis by these inhibitors involves a common step.
已分离出两株对25-羟胆固醇的杀伤作用具有抗性的中国仓鼠肺（Dede）细胞系，它们能在25-羟胆固醇存在的情况下生长至汇合。其中一株抗性细胞系在25-羟胆固醇浓度导致野生型细胞中这些功能几乎完全被抑制的情况下，仍表现出高至正常的生长速率以及正常水平的3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶（甲羟戊酸：NADP⁺氧化还原酶（辅酶A酰化），EC 1.1.1.34）活性和甾醇合成。另一变异细胞系对二醇对细胞生长、甾醇合成和HMG-CoA还原酶活性的抑制作用表现出部分抗性。当细胞在无选择剂的情况下培养时，抗性表型保持稳定。两株抗性细胞系中HMG-CoA还原酶的米氏常数（HMG-CoA）、热稳定性以及对Mg²⁺和ATP抑制的敏感性均未改变。在25-羟胆固醇存在下选择生长的这两株细胞系对7-酮胆固醇、20α-羟胆固醇以及血清对HMG-CoA还原酶和甾醇合成的抑制作用也具有抗性，这表明这些抑制剂对胆固醇合成的抑制涉及一个共同步骤。
